The proposed research deals with the ontogeny and phylogeny of the immune response and the machinery that generates it. In particular, amphibian model systems are and will be used exclusively to study the thymic origin of lymphocytes, the role of the thymic epithelium in educating lymphocytes for MHC restriction during their early ontogeny, the development of tolerance to self and nonself antigens during embryogenesis and larval life, the evolution of lymphocyte heterogeneity, and the phylogeny of MHC structure and function. Techniques used in these studies include hybridoma production, flow cytometry, immunocytochemistry, cell and tissue culture, microsurgery on amphibian embryos, cell and serum transfer, histology, and transplantation.